Bone health in breast cancer patients

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1 CAMPUS GROSSHADERN CAMPUS INNENSTADT KLINIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE DIREKTOR: PROF. DR. MED. SVEN MAHNER Bone health in breast cancer patients Nadia Harbeck Breast Center, University of Munich, Germany der Universität München Leitung: Prof. Nadia Harbeck

2 Bone health in breast cancer patients Bone health and breast cancer therapy Adjuvant use of bone stabilizing agents Treatment guidelines in MBC Open questions YOUR Questions Thanks to Prof. Peyman Hadji (Frankfurt) and Prof. Ralf Schmidmaier (Munich) for generously sharing their slides on short notice

3 LS-BMD (g/m 2 ) Age and Estrogen dependent Change of BMD and BT 1,2-1,1 - peak bone mass POSTMENOPAUSAL Estradiol Inh A, Inh B, FSH Act, BMP tone 1,0 - Preosteoclast 0,9-0,8-0 Puberty Fracture risk I I I I I I I I Abbreviations: Act, activin; BMP, bone morphogenetic protein; FSH, follicle-stimulating hormone; Inh, Inhibin. Years Preosteoblast Turnover Hadji P. et al. Ann Oncol (2012) 23(11): ; Adapted from Nicks KM, et al. Ann N Y Acad Sci. 2010;1192:

4 Breast Cancer Increases Fracture Risk Results of the WHI observational study Prospective cohort study with 5.1 years of follow-up 1 5,298 breast cancer survivors in WHI study 80,848 reference population with no history of cancer Adjustment for age, weight, and ethnicity Women with history of BC had a 31% increased risk of fracture Breast cancer Risk increase 31% Hazard ratio Decreased fractures Increased fractures WHI = Women s Health Initiative. 1. Chen Z, et al. Arch Intern Med. 2005;165:

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6 Fracture incidence of postmenopausal healthy and BC women on TAM and AI Schmidt N., Kostev K, Coleman RE and Hadji P. et al. Breast Cancer Res Treat Jan;155(1):151-7

7 ESMO clinical practice guideline: Bone health in cancer patients Clinicians treating cancer patients need to be aware of: Treatments to reduce skeletal morbidity in metastatic disease Strategies to minimise cancer treatmentinduced skeletal damage ESMO guidelines provide a framework for maintaining bone health in patients with cancer Coleman RE et al. Ann Oncol 2014;00:1 14.

8 Influence of Risedronate (OAW) on BMD in women with ER/PR pos Breast Cancer on AI Treatment Mean±SE percent change in bone mineral density in spine total hip, #p<0.05, ##p<0.01 for comparison between RIS (solid line) and placebo (dashed line) groups using linear mixed *p<0.05, **p<0.01 change from baseline using paired t test. Greenspan S.L. et al. Osteoporos Int (2015) 26:

9 Prevention of therapy-induced osteoporosis n=252, luminal EBC, adjuvant AI, -1.0 > T > Ellis et al, JCO 2008

10 Prevention of therapy-induced osteoporosis ABCSG-18: n=3420, luminal EBC, adjuvant AI Gnant et al, Lancet 2015

11 Prevention of therapy-induced bone loss Hadji et al, 2017

12 Prevention of therapy-induced bone loss Hadji et al, 2017

13 Bone-directed therapy in breast cancer patients Coleman et al, ESMO clinical practice guideline bone health in cancer patients (2014)

14 Bone metastases in animal models CK+ HER2+ tumor cells could be detected in the bone marrow already in the stage of atypical ductal hyperplasia. This spread is thus not a late event in tumor progression Hüsemann et al, Cancer Cell 2008

15 Disseminated tumor cells in the bone marrow of patients with EBC DTCs can already be detected in 30-40% of patients at time of primary diagnosis Presence of DTCs is associated with poor outcome Systemic chemotherapy cannot eliminate all DTCs Domschke et al, Ann Surg Oncol 2013; Janni et al, Clin Cancer Res 2011; Braun et al. N Engl J Med 2005; Becker et al, Breast Cancer Res Treat 2007; Janni W et al. Cancer

16 Zoledronic acid in EBC patients with DTCs Banys et al, BMC Cancer 2013

17 Optimal time to start zoledronic acid in EBC: ZO-FAST Coleman et al. Ann Oncol. 2013;24(2):

18 EBCTCG metaanalysis for adjuvant bisphosphonates EBCTCG, Lancet 2015

19 Recommendations of European Experts (2016): Bisphosphonates in EBC Hadji et al, Annals of Oncology, 2016

20 Bisphosphonates in EBC: Who benefits? Hadji et al, Annals of Oncology, 2016

21 Bone stabilizing agents in EBC: Denosumab Gnant et al, SABCS 2015

22 Bone stabilizing agents in EBC: Denosumab Gnant et al, SABCS 2015

23 Bone stabilizing agents in EBC: Denosumab Gnant et al, SABCS 2015

24 Bone health in cancer patients: ESMO guidelines Coleman et al, Annals of Oncology 2014

25 Bone health in cancer patients: ESMO guidelines Zometa Xgeva Bondronat Prolia Coleman et al, Annals of Oncology 2014

26 Bone health in cancer patients: ESMO guidelines Annals of Oncology 26 (supp 5), 2015

27 Bone health in EBC: EMA approvals for denosumab

28 Bone health in EBC: EMA approvals for denosumab HALT: hormone ablation therapy

29 Bone modifying agents in breast cancer Sukhbinder et al, 2017

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31 Bone health in breast cancer patients Bone health is an important issue in breast cancer patients due to natural changes and treatment induced bone loss (TIBL) Next to exercise, calcium and vitamin D, bone modifying agents (e.g. bisphosphonates, denosumab) are effective in reducing TIBL Adjuvant use of bone modifying agents (e.g. bisphosphonates, denosumab) is effective in reducing recurrences and thus prolonging DFS in postmenopausal patients. Body of evidence larger for adjuvant use of bisphosphonates with improvement of OS demonstrated in EBCTCG metaanalysis. Effective in postmenopausal patients irrespective of tumor biology, type of bisphosphonate. ABCSG 12 also demonstrated efficacy in premenopausal patients with ovarian suppression

32 EVIDENCE-BASED, PATIENT-ORIENTED BREAST CANCER THERAPY The Digital Diary for Every Patient Annually revised, evidence-based recommendations for diagnosis and treatment AGO (DKG, DGGG)